ERK and JNK activation is essential for oncogenic transformation by v-Rel.
In: Oncogene, Jg. 29 (2010-11-25), Heft 47, S. 6267-6279
Online
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Zugriff:
v-Rel is the acutely oncogenic member of the NF-κB family of transcription factors. Infection with retroviruses expressing v-Rel rapidly induces fatal lymphomas in birds and transforms primary lymphocytes and fibroblasts in vitro. We have previously shown that AP-1 transcriptional activity contributes to v-Rel-mediated transformation. Although v-Rel increases the expression of these factors, their activity may also be induced through phosphorylation by the mitogen-activated protein kinases (MAPKs). The expression of v-Rel results in the strong and sustained activation of the ERK and JNK MAPK pathways. This induction is critical for the v-Rel-transformed phenotype, as suppression of MAPK activity with chemical inhibitors or small interfering RNA severely impairs colony formation of v-Rel-transformed lymphoid cell lines. However, signaling must be maintained within an optimal range in these cells, as strong additional activation of either pathway beyond the levels induced by v-Rel through the expression of constitutively active MAPK proteins attenuates the transformed phenotype. MAPK signaling also has an important role in the initial transformation of primary spleen cells by v-Rel, although distinct requirements for MAPK activity at different stages of v-Rel-mediated transformation were identified. We also show that the ability of v-Rel to induce MAPK signaling more strongly than c-Rel contributes to its greater oncogenicity. [ABSTRACT FROM AUTHOR]
Titel: |
ERK and JNK activation is essential for oncogenic transformation by v-Rel.
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Autor/in / Beteiligte Person: | Kralova, J ; Sheely, J I ; Liss, A S ; Bose, H R |
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Zeitschrift: | Oncogene, Jg. 29 (2010-11-25), Heft 47, S. 6267-6279 |
Veröffentlichung: | 2010 |
Medientyp: | academicJournal |
ISSN: | 0950-9232 (print) |
DOI: | 10.1038/onc.2010.359 |
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